Epigenetic Alteration in Adult Male Testes after Perinatal Exposure to di-(2-ethylhexyl) Phthalate

Among phthalates, di-(2-ethylhexyl) phthalate (DEHP) is commonly used to increase the flexibility of plastic products including food packaging, toys, and medical devices [1]. Due to the wide use of phthalate in consumer products, humans may be exposed to DEHP through ingestion, skin contact, and inhalation during their lifetime. Exposure to DEHP during the developmental period could induce long-lasting adverse effects in adult reproductive function [2,3]. Analysis of DNA methylation, the most well-known mechanism of epigenetic regulation, might help in the understanding of the development of adult onset disease. Previously, DNA methylation was increased in fetuses after maternal exposure to DEHP [4,5]. Hypermethylation and hypo methylation of DNA are associated with the production of oxidative radicals [6]. DEHP induced apoptosis in germ cells by increasing oxidative radicals [7]. Once the production of oxidative radicals is increased, defense mechanisms would start to maintain an adequate homeostasis. To predict the oxidative damage after perinatal exposure to DEHP in adult male rat offspring, clusterin mRNA and protein expression were analyzed. Clusterin has molecular chaperone properties that facilitate inhibition of oxidative stress or cellular oxidative injury, and can be used as a potent cellular marker of oxidative stress [8]. The analysis of clusterin expression and DNA methylation in its promoter region in adult rat offspring might help to understand the biological plausibility of perinatal exposure to DEHP and long-lasting effects on testicular function. Therefore, in the present study, the expression of clusterin and steroidogenic enzymes in rat testes was examined to investigate the adverse effects on testicular function. In addition, the global DNA methylation and methylation of clusterin promoter region was analyzed to evaluate the long-lasting effects on adult testes after perinatal exposure to DEHP.

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